Ginsenoside Compound K

The roots of Panax ginseng C.A.Mey.

Ginsenoside C-K, a bacterial metabolite of G-Rb1, exhibits anti-inflammatory effects by reducing iNOS and COX-2. Ginsenoside C-K exhibits an inhibition against the activity of CYP2C9 and CYP2A6 in human liver microsomes with IC50s of 32.0±3.6 μM and 63.6±4.2 μM, respectively.

In Vitro:Ginsenoside C-K, a bacterial metabolite of G-Rb1, exhibits anti-inflammatory effects mainly by reducing inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and proinflammatory cytokines. Ginsenoside C-K suppresses the expression of proinflammatory cytokines by downregulating the activities of IRAK-1, MAPKs, IKK-α, and NF-κB in LPS-treated murine peritoneal macrophages. Ginsenoside C-K also suppresses the expression of iNOS and COX-2 by inhibiting NF-κB signaling in LPS-stimulated RAW264.7 cells. In zymosan-treated bone-marrow-derived macrophages (BMDMs) and RAW264.7 cells, Ginsenoside C-K inhibits inflammatory responses by negatively regulating the secretion of proinflammatory cytokines, the activation of MAPKs, and the generation of ROS. In addition, anti-inflammatory activity of Ginsenoside C-K has been observed in LPS-stimulated microglial cells. Ginsenoside C-K hinders inflammatory responses by controlling both the generation of ROS and the activities of MAPKs, NF-κB, and AP-1[1]. Ginsenoside C-K, a major metabolite of ginsenosides in the gastrointestinal tract, inhibits NF-κB signaling in a PXR-dependent manner. Ginsenoside C-K is shown to promote recovery of dextran sulfate sodium (DSS) -induced colitis by suppressing NF-κB activation. Ginsenoside C-K significantly reduces TNF-α-induced upregulation of IL-1β and iNOS mRNA levels, and restores the mRNA levels of PXR and CYP3A4 in LS174T cells[2]. Ginsenoside C-K, one of the intestinal metabolites of 20(S)-protopanaxadiol derivatives, exhibits an inhibition against the activity of CYP2C9 in human liver microsomes with an IC50 value of 32.0±3.6 μM, a weak inhibition against the activity of CYP2A6 in human liver microsomes with an IC50 value of 63.6±4.2 μM, and an even weaker inhibition against the activity of CYP2D6 in human liver microsomes with an IC50 value of more than 100 μM[4].

In Vivo:The weight of the collagen-induced arthritis (CIA) mice increases slowly and is significantly less than that of the normal DBA/1 mice beginning on d 3 after injection of the emulsion. Ginsenoside C-K (28, 56, and 112 mg/kg) mice recover their weight by d 32 after the emulsion injection. Ginsenoside C-K (56 and 112 mg/kg) and Methotrexate (MTX)-treated (2 mg/kg) mice show significantly increased body weight on d 50 as compared with CIA mice. Hind paw-swelling began on d 24 post-immunization. CIA mice are treated from d 28 to d 50. Arthritis scores are measured every 4 d beginning on d 24. Ginsenoside C-K (56 and 112 mg/kg) significantly reduces the arthritis scores of the mice on d 51[3].

References:
[1]. Kim JH, et al. Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responsesand diseases. J Ginseng Res. 2017 Oct;41(4):435-443. [2]. Zhang J, et al. Ginsenosides Regulate PXR/NF-κB Signaling and Attenuate Dextran Sulfate Sodium-Induced Colitis. Drug Metab Dispos. 2015 Aug;43(8):1181-9. [3]. Liu KK, et al. Ginsenoside compound K suppresses the abnormal activation of T lymphocytes in mice with collagen-induced arthritis. Acta Pharmacol Sin. 2014 May;35(5):599-612. [4]. Liu Y, et al. Ginsenoside metabolites, rather than naturally occurring ginsenosides, lead to inhibition of human cytochrome P450 enzymes. Toxicol Sci. 2006 Jun;91(2):356-64.

A review of biotransformation and pharmacology of ginsenoside compound K.[Pubmed:25449425]

Fitoterapia. 2015 Jan;100:208-20.

As an intestinal bacterial metabolite of ginseng protopanaxadiol saponins, Ginsenoside Compound K (20-O-beta-d-glucopyranosyl-20(S)-protopanaxadiol, CK) is a major deglycosylated metabolite form of ginsenosides which is absorbed into the systemic circulation. And it has demonstrated such diverse intriguing biological properties as anticarcinogenic, anti-inflammation, antiallergic, anti-diabetic, anti-angiogenesis, anti-aging, neuroprotective and hepatoprotective effects. The present review shall summarize recent studies on various biotransformation and pharmacological activities of CK.

Ginsenoside compound K promotes beta-amyloid peptide clearance in primary astrocytes via autophagy enhancement.[Pubmed:25187838]

Exp Ther Med. 2014 Oct;8(4):1271-1274.

The aim of the present study was to investigate the effect of Ginsenoside Compound K on beta-amyloid (Abeta) peptide clearance in primary astrocytes. Abeta degradation in primary astrocytes was determined using an intracellular Abeta clearance assay. Aggregated LC3 in astrocyte cells, which is a marker for the level of autophagy, was detected using laser scanning confocal microscope. The effect of compound K on the mammalian target of rapamycin (mTOR)/autophagy pathway was determined using western blot analysis, and an enzyme-linked immunosorbent assay was used for Abeta detection. The results demonstrated that compound K promoted the clearance of Abeta and enhanced autophagy in primary astrocytes. In addition, it was found that phosphorylation of mTOR was inhibited by compound K, which may have contributed to the enhanced autophagy. In conclusion, compound K promotes Abeta clearance by enhancing autophagy via the mTOR signaling pathway in primary astrocytes.

Ginsenoside compound K-bearing glycol chitosan conjugates: synthesis, physicochemical characterization, and in vitro biological studies.[Pubmed:25129755]

Carbohydr Polym. 2014 Nov 4;112:359-66.

Ginsenosides are triterpenoids found in Panax ginseng and have a numerous structural, functional, and pharmacological properties. The purpose of this study was to develop hydrophilic polymer functionalized ginsenoside conjugates to enhance water solubility and targeted delivery. To this end, hydrophobic Ginsenoside Compound K (CK) was covalently conjugated to the backbone of hydrophilic glycol chitosan (GC) through an acid-labile linkage. The resulting GC-CK conjugates formed self-assembled spherical nanoparticles in an aqueous solution, and their particles sizes were (296 nm and 255 nm) dependent on the degree of CK substitution. The nanoparticles were stable in the physiological buffer (pH 7.4) over a period of 8 days, whereas they were readily degraded under acidic conditions (pH 5.0) mimicking the intracellular pH-conditions. From in vitro release experiment, it was found that CK released slowly from the self-assembled nanoparticles in the physiological buffer (pH 7.4). On the other hand, the release rate of CK was rapidly increased under the acidic condition (pH 5.0). In vitro cytotoxicity assays revealed that GC-CK conjugates exhibited higher cytotoxicity than CK in HT29, and similar cytotoxicity in HepG2, and HT22 cell lines. Moreover, RAW264.7 cells treated with GC-CK maintained good cell viability and exhibited decreased lipopolysaccharide-induced NO production. Taken together, these results suggest that the GC-CK conjugate may be potentially useful as a tumor-specific delivery vehicle.

Ginsenoside compound K attenuates metastatic growth of hepatocellular carcinoma, which is associated with the translocation of nuclear factor-kappaB p65 and reduction of matrix metalloproteinase-2/9.[Pubmed:20979019]

Planta Med. 2011 Mar;77(5):428-33.

The intestinal metabolite of ginseng saponin, compound K (CK), has various chemopreventive and chemotherapeutic activities, including anti-tumor activity. However, the functional mechanisms through which CK attenuates metastatic growth in hepatocellular carcinoma (HCC) remain unclear. Here, using multiple IN VITRO and IN VIVO models, we reported that CK strongly attenuated colony formation, adhesion, and invasion of HCC cells IN VITRO and dramatically inhibited spontaneous HCC metastatic growth IN VIVO. At the molecular level, immunofluorescence and Western blotting analysis confirmed that inhibition of metastatic growth of HCC induced by CK treatment caused a time-dependent decrease in nuclear NF- kappaB p65 and a concomitant increase in cytosolic NF- kappaB p65, indicating that CK suppressed the activation of the NF- kappaB pathway. Meanwhile, our study showed that the inhibition of matrix metalloproteinase2/9 (MMP2/9) expression caused by CK treatment was associated with NF- kappaB p65 nuclear export. Taken together, our results not only revealed that NF- kappaB p65 nuclear export and the reduction of MMP2/9 expression were associated with the metastatic inhibition induced by CK, but also suggested that CK may become a potential cytotoxic drug in the prevention and treatment of HCC.

Ginsenoside compound K, not Rb1, possesses potential chemopreventive activities in human colorectal cancer.[Pubmed:22426808]

Int J Oncol. 2012 Jun;40(6):1970-6.

Ginsenoside Compound K (C-K) is an intestinal microbiota metabolite of ginsenoside Rb1, a major constituent in American ginseng. However, previous ginseng anti-cancer observations were largely focused on ginseng parent compounds but not metabolites, and anti-colorectal cancer studies on C-K were limited. This study investigated the anti-proliferative effects of C-K when compared to those of Rb1, and the related mechanisms of action, in HCT-116 and SW-480 colorectal cancer cells. The effects of Rb1 and C-K on the proliferation of HCT-116 and SW-480 human colorectal cancer cells were compared using an MTS assay. Cell cycle and cell apoptosis were assayed using flow cytometry. Enzymatic activities of caspases were determined by colorimetric assay, and interactions of C-K and caspases were explored by docking analysis. C-K showed significant anti-proliferative effects in HCT-116 and SW-480 cells at concentrations of 30-50 microM. At the same concentrations, Rb1 did not show any effects, while C-K arrested the cells in the G1 phase, and significantly induced cell apoptosis. Compared to HCT-116 (p53 wild-type), the p53 mutant cell line SW-480 was more sensitive to C-K as assessed by cell cycle regulation and apoptosis induction. C-K activated expression of caspases 8 and 9, consistent with docking analysis. The docking data suggested that C-K forms hydrogen bonds with Lys253, Thr904 and Gly362 in caspase 8, and with Thr62, Ser63 and Arg207 in caspase 9. C-K, but not its parent ginsenoside Rb1, showed significant anti-proliferative and pro-apoptotic effects in human colorectal cancer cells. These results suggest that C-K could be a potentially effective anti-colorectal cancer agent.

Ginsenoside compound K inhibits angiogenesis via regulation of sphingosine kinase-1 in human umbilical vein endothelial cells.[Pubmed:24687256]

Arch Pharm Res. 2014;37(9):1183-92.

Ginsenoside Compound K (CK) is a metabolite of the protopanaxadiol-type saponins of Panax ginseng C.A. Meyer (Araliaceae), has long been used to treat against the development of cancer, inflammation, allergies, and diabetes. This study examined the anti-angiogenic properties of CK against sphingosine 1-phosphate (S1P)-induced cell migration via regulation of sphingosine kinase 1 (SPHK1) in human umbilical vein endothelial cells (HUVEC). Studies on S1P-induced cell migration, expression of SPHK1 and MMPs and analysis of sphingolipid metabolites by LC-MS/MS were examined after the treatment of CK (2.5, 5, 10 mug/mL) in HUVEC. S1P produced by SPHK1 is also involved in cell growth, migration, and protection of apoptosis; therefore, we sought to investigate whether ginsenosides are able to regulate SPHK1. For this purpose, we developed an inhibitory assay of SPHK1 activity and an analytical method for detection of S1P and other sphingolipid metabolites in HUVEC. Ginsenoside CK inhibited 100 nM S1P-induced cell migrations in a dose-dependent manner. Among tested ginsenosides, CK exclusively inhibited S1P production, SPHK1 activity and SPHK1 expression in HUVEC, whereas expression of the pro-apoptotic sphingolipids, sphingosine and ceramide, was increased in response to CK. The major subspecies of the increased ceramide was C24:0-ceramide. CK also disrupted the sphingolipid rheostat, which ultimately influences cell fate, and dose-dependently inhibited HUVEC migration by reducing expression of metalloproteinases (MMPs). Ginsenoside CK acts as a unique HUVEC migration inhibitor by regulating MMP expression, as well as the activity of SPHK1 and its related sphingolipid metabolites.

Ginsenoside C-K, a bacterial metabolite of G-Rb1, exhibits anti-inflammatory effects by reducing iNOS and COX-2. Ginsenoside C-K exhibits an inhibition against the activity of CYP2C9 and CYP2A6 in human liver microsomes with IC50s of 32.0±3.6 μM and 63.6±4.2 μM, respectively.

Ginsenoside Compound K,39262-14-1,Ginsenoside K; Ginsenoside compound K,Natural Products, buy Ginsenoside Compound K , Ginsenoside Compound K supplier , purchase Ginsenoside Compound K , Ginsenoside Compound K cost , Ginsenoside Compound K manufacturer , order Ginsenoside Compound K , high purity Ginsenoside Compound K